Technetium-99m (Tc-99m) is the most commonly used radioisotope in nuclear medicine. Typically, Tc-99m is obtained from Mo-99/Tc-99m generator systems, which are self-contained systems housing a parent (Mo-99)-daughter (Tc-99m) mixture in equilibrium. Commercially, molybdenum-99 is produced in a high-flux nuclear reactor from the irradiation of highly-enriched uranium targets (93% Uranium-235) and shipped to generator manufacturing sites. Mo-99/Tc-99m generators are then distributed from these centralized locations to hospitals and pharmacies through-out the country. Because the number of production sites are limited, and compounded by the limited number of available high flux nuclear reactors, the supply of Mo-99 is susceptible to frequent interruptions and shortages resulting in delayed nuclear medicine procedures.
To try and address this problem, alternative methods of producing Mo-99 and/or Tc-99 are being undertaken. Because Mo-99 has a 2.7 day half-life, which allows for country-wide distribution, most efforts have focused on producing Mo-99. For example, three standard approaches toward the formation of Mo-99 include:235U92+1n0→99Mo42+x1n0+many other nuclei  (1)98Mo42+1n0→99Mo42+γ  (2)100Mo42+γ→99Mo42+1n0  (3)
Other approaches have considered directly producing Tc-99m, which has a 6 hour half-life, for local use. The Mo-100(p,2n)Tc-99m reaction (see Equation 4) is one method under investigation where a conventional electroplated, compacted powder or melted solid target is irradiated with a proton beam, such as that provided by a cyclotron, and subsequently processed to isolate Tc-99m from the target matrix.100Mo42+1H1→99mTc43+21n0  (4)
Positron emission tomography (PET) cyclotrons are in widespread use at hospitals, pharmacies, mobile PET and other facilities, and therefore are an attractive source of energetic protons. However, the solid target approach is cumbersome and not well-suited for in-house hospital locations where automated chemistry is highly desired. For example, isolating technetium from solid molybdenum requires oxidative dissolution of the metallic target and separation of the chemical species. Thus, while large yields are potentially possible with this method, delays in processing and intensive handling/processing could cause substantial decay losses and increased processing costs.
In addition to the wide-spread availability of PET cyclotrons, these systems are generally fitted with commercially-available F-18 production targets and automated chemistry systems to manufacture fluorinated deoxyglucose (FDG). The F-18 production target is a cylindrical, conical or similar hollow container filled with H218O which is irradiated with a proton beam and forms F-18 by the nuclear reaction 18O(p,n)18F. The irradiated water is transferred to the automated chemistry system, which extracts the 18F and produces the desired end product, 18FDG, in a Good Manufacturing Practices (GMP) environment ready for clinical use. However, a viable method that can take advantage of the foregoing attributes of PET cyclotron FDG systems to prepare Tc-99m does not currently exist.
Accordingly, new methods of generating Tc-99m with a PET cyclotron (or a similar accelerator) and associated targetry and chemistry systems are needed.